title: Anxiolytic effects of vestipitant in a sub-group of healthy volunteers known to be sensitive to CO2 challenge.
abstract: The pharmacological properties of two NK1 antagonists were studied in comparison with a benzodiazepine during a 7% CO2 challenge in a population of healthy volunteers selected for a high sensitivity to the challenge. In total, 19 healthy subjects, pre-screened for their responsiveness to the 7% CO2 test, took part in the randomised, double-blind, cross-over, incomplete block design study. After receiving treatment or placebo, the volunteers were subjected to three 7% CO2 challenges each for a time of 20 min. The treatment consisted of the administration of the following three active drugs: a single dose of benzodiazepine alprazolam (0.75 mg) and a single dose of the NK1 antagonists vestipitant (GW597599) (15 mg) and vofopitant (GR205171) (25 mg). Anxiety during the challenge was evaluated with Visual Analogue Scale-Anxiety (VAS-A) and with Panic Symptom List (PSL III-R). Respiratory parameters, heart rate and skin conductance were also recorded. Compared with placebo, vestipitant showed a significant reduction (p<0.05) in anxiety assessed on the VAS-A scale (ΔVAS-A%) while alprazolam significantly (p<0.01) attenuated the PSL III-R total score. Vofopitant did not show any anxiolytic effect. In the comparison analysis between placebo and drugs, none of the respiratory and other physiological parameters showed a statistically significant difference.
authors.affiliation: 1Department of Neuroscience, University of Padova, Italy.
authors.forename: Stefano Zanone
authors.initials: SZ
authors.lastname: Poma
authors.forename: Emilio
authors.initials: E
authors.lastname: Merlo-Pich
authors.forename: Paolo
authors.initials: P
authors.lastname: Bettica
authors.forename: Massimo
authors.initials: M
authors.lastname: Bani
authors.forename: Paolo
authors.initials: P
authors.lastname: Fina
authors.forename: Luigi
authors.initials: L
authors.lastname: Ziviani
authors.forename: Stefano
authors.initials: S
authors.lastname: Milleri
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000627:therapeutic use; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy*; D001008:Anxiety Disorders / Q000188:drug therapy*; D001569:Benzodiazepines / Q000627:therapeutic use; D002245:Carbon Dioxide / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D010880:Piperidines / Q000627:therapeutic use*; D013777:Tetrazoles / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D005464:Fluorobenzenes; D010880:Piperidines; D013777:Tetrazoles; D001569:Benzodiazepines; D002245:Carbon Dioxide; C103207:vofopitant; C534550:vestipitant; D000525:Alprazolam
keywords: Healthy volunteers; NK1 antagonists; alprazolam; carbon dioxide; vestipitant